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@ARTICLE{Jocher:277534,
      author       = {Jocher, Georg and Ozcelik, Gozde and Müller, Stephan A and
                      Hsia, Hung-En and Lastra Osua, Miranda and Hofmann, Laura I
                      and Aßfalg, Marlene and Dinkel, Lina and Feng, Xiao and
                      Schlepckow, Kai and Willem, Michael and Haass, Christian and
                      Tahirovic, Sabina and Blobel, Carl P and Lichtenthaler,
                      Stefan F},
      title        = {{T}he late-onset {A}lzheimer’s disease risk factor
                      {RHBDF}2 is a modifier of microglial {TREM}2 proteolysis},
      journal      = {Life science alliance},
      volume       = {8},
      number       = {5},
      issn         = {2575-1077},
      address      = {Heidelberg},
      publisher    = {EMBO Press},
      reportid     = {DZNE-2025-00430},
      pages        = {e202403080},
      year         = {2025},
      abstract     = {The cell surface receptor TREM2 is a key genetic risk
                      factor and drug target in Alzheimer’s disease (AD). In the
                      brain, TREM2 is expressed in microglia, where it undergoes
                      proteolytic cleavage, linked to AD risk, but the responsible
                      protease in microglia is still unknown. Another
                      microglial-expressed AD risk factor is catalytically
                      inactive rhomboid 2 (iRhom2, RHBDF2), which binds to and
                      acts as a non-catalytic subunit of the metalloprotease
                      ADAM17. A potential role in TREM2 proteolysis is not yet
                      known. Using microglial-like BV2 cells, bone
                      marrow–derived macrophages, and primary murine microglia,
                      we identify iRhom2 as a modifier of ADAM17-mediated TREM2
                      shedding. Loss of iRhom2 increased TREM2 in cell lysates and
                      at the cell surface and enhanced TREM2 signaling and
                      microglial phagocytosis of the amyloid β-peptide (Aβ).
                      This study establishes ADAM17 as a physiological TREM2
                      protease in microglia and suggests iRhom2 as a potential
                      drug target for modulating TREM2 proteolysis in AD.},
      cin          = {AG Lichtenthaler / AG Tahirovic / AG Haass},
      ddc          = {570},
      cid          = {I:(DE-2719)1110006 / I:(DE-2719)1140003 /
                      I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40081988},
      doi          = {10.26508/lsa.202403080},
      url          = {https://pub.dzne.de/record/277534},
}